Although sleep disorders have been identified by the NIH as an area with tremendous scientific growth potential there are a paucity of patient oriented investigators studying sleep-related questions. The University of Pennsylvania is fortunate to have internationally recognized faculty and a strong infrastructure to support high quality patient-oriented research and training m sleep disorders. This infrastructure includes: Center for Sleep and Respiratory Neurobiology, Center for Clinical Epidemiology and Biostatistics, General Clinical Research Center, 3 Sleep Training Grants and the Pulmonary Imaging Group. Dr. Schwab is an integral part of each of these programs and is highly committed to a career in patient-oriented sleep research, proposing to study the genetics and biomechanical basis for obstructive sleep apnea. Dr. Schwab has made seminal observations about changes in the upper airway in patients with sleep apnea and he has successfully mentored several pulmonary fellows and junior faculty. Dr. Schwab through funding from this K24 can further develop into an academic leader and train others investigators that the sleep field desperately needs. Specifically this award would allow Dr. Schwab to develop further expertise in new radiologic techniques in upper airway imaging and computer-based volumetric analysis; further his expertise in genetic epidemiology and bioinformatics; allow increased time for mentoring young scientists and for developing new areas of collaboration with scientists. Dr. Schwab has developed a state-of-the-art upper airway imaging program focusing on understanding the pathogenesis and treatment of obstructive sleep apnea. Recently, Dr. Schwab has begun to apply his upper airway imaging expertise to study phenotypic risk factors for sleep apnea. He is the first to apply advanced quantitative MR Imaging techniques and novel volumetric computer image analysis techniques to study the genetic basis for sleep apnea. The scientific portion of this grant will utilize upper airway imaging to study both the pathogenesis and genetics of sleep apnea. My specific aims are: 1) to evaluate and compare upper airway soft tissue structural and biomechanical properties in apneics and normal weight-matched controls during wakefulness and sleep; 2) to quantify upper airway craniofacial structure, soft tissues and regional fat deposition using three dimensional magnetic resonance imaging in order to determine the intermediate traits associated with obstructive sleep apnea utilizing a case control design in normals and apneics ; and 3) to determine the upper airway structural risk factors for sleep apnea that demonstrate family aggregation and are most likely to have a genetic component by comparing probands, siblings of probands, neighborhood controls and siblings of neighborhood controls. To address these specific aims, we have planned a logical series of studies that will provide insight in the pathogenesis of obstructive sleep apnea and the anatomic risk factors for this condition.